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Paracoccidioidomycosis is an infection with the potential for environmental dissemination, especially in regions of hot and humid climate, where human cases have been recorded in the Southwestern Amazon of Brazil, specifically in the state of Acre. Despite studies providing information about the presence of these fungi in soil and animal samples, such as armadillos, further investigations are still needed to determine the epidemiological distribution of the genus Paracoccidioides. The aim of this study was to detect the occurrence of Paracoccidioides fungi in the Southwestern Amazon. To achieve this, 60 soil samples were collected from armadillo burrows on rural properties in the in the municipalities of Acrelândia, Bujari, Plácido de Castro, Rio Branco, Sena Madureira, and Senador Guiomard, located in the state of Acre, Brazil. Fungal DNA was extracted from these samples using the DNEASY® PowerSoil kit-Quiagen, followed by Nested PCR technique with ITS4 and ITS5 as external primers, and PBITS-E and PBITS-R as internal primers. DNA amplification products of about 380 bp compatible with Paracoccidioides spp. were detected in six samples (10%), being sequenced and identified as P. brasiliensis. These findings indicate that the soils of the Acre state could be considered a potential source for Paracoccidioides spp., suggesting that local infections are likely., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Paracoccidioides species have always been surrounded by taxonomic uncertainties. The continuing nomenclatoral muddle was caused in part by the failure of Adolfo Lutz and Jorge Lôbo to name the etiologic agents of human paracoccidioidomycosis and Jorge Lôbo's diseases, respectively. Early in their history, it was postulated that the cultivable species causing systemic infections belonged in the genus Paracoccidioides, whereas the uncultivable species, causing skin disease, were not part of the genus. The taxonomy of these pathogens was further complicated when a similar skin disease with numerous yeast-like cells in infected dolphins was also reported. Due to its phenotypic similarities with that described by Jorge Lôbo in human and its uncultivable nature, it was assumed that the disease in dolphins was caused by the same fungus. Recent molecular and population genetic analysis, however, found the DNA extracted from the uncultivable yeast-like cells affecting dolphins shared common phylogenetic traits with cultivable Paracoccidioides species. The study revealed that the uncultivable pathogens comprised 2 different Paracoccidioides species, now known as P. ceti and P. loboi, correspondingly. To validate P. loboi binomial, a comprehensive historical critical review of Jorge Lôbo etiology was performed. This review showed the proposed binomial P. loboi was previously used, and, thus, a replacement name is introduced, Paracoccidioides lobogeorgii nom. nov. In addition, in this review, several cultivable human Paracoccidioides species are validated, and the generic type species, P. brasiliensis, is neotypified as the original material could not be traced., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Vilela et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Armadillos are specialist diggers and their burrows are used to find food, seek shelter and protect their pups. These burrows can also be shared with dozens of vertebrate and invertebrate species and; consequently, their parasites including the zoonotics. The aim of this study was to diagnose the presence of zoonotic parasites in four wild-caught armadillo species from two different Brazilian ecosystems, the Cerrado (Brazilian savanna) and the Pantanal (wetland). The investigated parasites and their correspondent diseases were: Toxoplasma gondii (toxoplasmosis), Trypanosoma cruzi (Chagas disease), Leishmania spp., (leishmaniasis), Paracoccidioides brasiliensis (Paracoccidioidomicosis) and Mycobacterium leprae (Hansen's disease). Forty-three free-living armadillos from Pantanal and seven road-killed armadillos from the Cerrado were sampled. Trypanosoma cruzi DTU TcIII were isolated from 2 out of 43 (4.65%) armadillos, including one of them also infected with Trypanosoma rangeli. Antibodies anti-T. gondii were detected in 13 out of 43 (30.2%) armadillos. All seven armadillos from Cerrado tested positive for P. brasiliensis DNA, in the lungs, spleen, liver fragments. Also, by molecular analysis, all 43 individuals were negative for M. leprae and Leishmania spp. Armadillos were infected by T. cruzi, T. rangeli, P. brasiliensis and presented seric antibodies to T. gondii, highlighting the importance of those armadillos could have in the epidemiology of zoonotic parasites., (© 2020 Wiley-VCH GmbH.)

Paracoccidioidomycosis caused by Paracoccidioides lutzii is endemic in the Midwest of Brazil and its clinical spectrum is still little known due to the recent identification of this fungal species. A patient resident in Southeast Brazil, but who had lived for many years in the Midwest region, presented with skin injuries, chronic cough and bilateral adrenal involvement. Paracoccidioides spp. was isolated in culture from a skin lesion biopsy. This isolate was later identified as P. lutzii using gene sequencing. A favorable initial response to treatment with itraconazole was observed, but a few weeks later, the patient developed respiratory failure and worsening of lung lesions. Evaluation by computed tomography and echocardiography were suggestive of pulmonary arterial hypertension, and a bronchoscopic biopsy showed peribronchial remodeling. The patient completed the antifungal treatment but maintained the respiratory dysfunction. The reported case shows that P. lutzii can be isolated from patients in a geographic area far from the place of infection acquisition and that, as P. brasiliensis , it can cause adrenal injury and cardio-respiratory complications as a consequence of excessive necrosis and fibrosis.

Paracoccidioides brasiliensis and the related species P. americana, P. restrepiensis, P. venezuelensis, and P. lutzii (Ascomycota, Ajellomycetaceae) are the etiological agents of paracoccidoidoimycosis (PCM), one of the most important systemic mycoses in Latin America. They are dimorphic fungi, with a mycelial life cycle in soil and a yeast phase associated with tissues of mammalian hosts. This study aimed to detect Paracoccidioides spp. in armadillo tissues and associated soil samples in three well-defined geographic areas, including the Alta Floresta, an area not only endemic for PCM in the central region of Brazil but also of probable P. lutzii occurrence, whose ecology and geographic distribution are poorly elucidated. The isolates were genotyped by sequencing ITS-rDNA and the gp43-exon-2 region, and by PCR-RFLP of alpha tubulin (tub1) gene; mycological aspects such as yeast-to-mycelial transition, growth and conidial production in soil extract agar were also evaluated. We confirmed that while armadillos are highly infected by P. brasiliensis, including multiple infections by distinct genotypes or species (P. brasiliensis and P. americana) in the same animal, the same does not hold true for P. lutzii, which in turn seems to present less capacity for mycelial growth and conidial production, when developing in a soil-related condition.

Paracoccidioidomycosis is a systemic fungal disease associated with agricultural activities. Its incidence and prevalence are underestimated because of the lack of reporting in several Brazilian states. If paracoccidiodomycosis is not diagnosed and treated early and adequately, endemic fungal infection may result in serious sequelae. In addition to the Paracoccidioides brasiliensis (P. brasiliensis) complex, the appearance of a new species, Paracoccidioides lutzii (P. lutzii), in Rondônia state, where the disease has reached epidemic levels, and in the country's Midwest region and Pará state, are challenges to diagnosis and to the urgent availability of antigens that are reactive with patients' sera. These guidelines aim to update the first Brazilian consensus on paracoccidioidomycosis by providing evidence-based recommendations for bedside patient management. The guidelines provide data on etiology, epidemiology, immunopathogenesis, diagnosis, treatment and sequelae, with emphasis on diagnosis and treatment, as well as current recommendations and challenges in this field of knowledge.

Paracoccidioidomycosis is a systemic fungal disease occurring in Latin America that is associated with rural environments and agricultural activities. However, the incidence and prevalence of paracoccidiodomycosis is underestimated because of the lack of compulsory notification. If paracoccidiodomycosis is not diagnosed and treated early and adequately, the endemic fungal infection could result in serious sequelae. While the Paracoccidioides brasiliensis ( P. brasiliensis ) complex has been known to be the causal agent of paracoccidiodomycosis, a new species, Paracoccidioides lutzii ( P. lutzii ), has been reported in Rondônia, where the disease has reached epidemic levels, and in the Central West and Pará. Accurate diagnoses and availability of antigens that are reactive with the patients' sera remain significant challenges. Therefore, the present guidelines aims to update the first Brazilian consensus on paracoccidioidomycosis by providing evidence-based recommendations for bedside patient management. This consensus summarizes etiological, ecoepidemiological, molecular epidemiological, and immunopathological data, with emphasis on clinical, microbiological, and serological diagnosis and management of clinical forms and sequelae, as well as in patients with comorbidities and immunosuppression. The consensus also includes discussion of outpatient treatments, severe disease forms, disease prevalence among special populations and resource-poor settings, a brief review of prevention and control measures, current challenges and recommendations.

We aimed to evaluate whether the occurrence of cryptic species of Paracoccidioides brasiliensis, S1, PS2, PS3 and Paracoccidioides lutzii, has implications in the immunodiagnosis of paracoccidioidomycosis (PCM). Small quantities of the antigen gp43 were found in culture filtrates of P. lutzii strains and this molecule appeared to be more variable within P. lutzii because the synonymous-nonsynonymous mutation rate was lower, indicating an evolutionary process different from that of the remaining genotypes. The production of gp43 also varied between isolates belonging to the same species, indicating that speciation events are important, but not sufficient to fully explain the diversity in the production of this antigen. The culture filtrate antigen AgEpm83, which was obtained from a PS3 isolate, showed large quantities of gp43 and reactivity by immunodiffusion assays, similar to the standard antigen (AgB-339) from an S1 isolate. Furthermore, AgEpm83 was capable of serologically differentiating five serum samples from patients from the Botucatu and Jundiaí regions. These patients had confirmed PCM but, were non-reactive to the standard antigen, thus demonstrating an alternative for serological diagnosis in regions in which S1 and PS2 occur. We also emphasise that it is not advisable to use a single antigen preparation to diagnose PCM, a disease that is caused by highly diverse pathogens.

Taking into account that paracoccidioidomycosis infection occurs by inhalation of the asexual conidia produced by Paracoccidioides spp. in its saprobic phase, this work presents the collection of aerosol samples as an option for environmental detection of this pathogen, by positioning a cyclonic air sampler at the entrance of armadillo burrows. Methods included direct culture, extinction technique culture and Nested PCR of the rRNA coding sequence, comprising the ITS1-5.8S-ITS2 region. In addition, we evaluated one armadillo (Dasypus novemcinctus) as a positive control for the studied area. Although the pathogen could not be isolated by the culturing strategies, the aerosol sampling associated with molecular detection through Nested PCR proved the best method for discovering Paracoccidioides spp. in the environment. Most of the ITS sequences obtained in this investigation proved to be highly similar with the homologous sequences of Paracoccidioides lutzii from the GenBank database, suggesting that this Paracoccidioides species may not be exclusive to mid-western Brazil as proposed so far.

Paracoccidioidomycosis (PCM) is a severe systemic mycosis, endemic in Latin America and highly prevalent in Brazil, where it ranks eighth as a mortality cause among infectious and parasitic diseases in humans. The disease in animals has been little explored. It is observed that armadillos can harbor the fungus at high frequencies, although the active disease has not been well documented in this wild mammal. Dogs are susceptible to experimental infection, and the naturally acquired PCM-disease was reported only recently in a dog from Brazil. The present work reports the second case of naturally acquired PCM in a 6-year-old female dog that presented emaciation, lymphadenomegaly, and hepatosplenomegaly. Biochemical and pulmonary radiographic evaluation did not reveal any abnormalities. PCM was diagnosed by clinical findings, culturing, immunohistochemistry, and histopathology of popliteal lymph node. The fungus was recovered from popliteal lymph node, and the molecular analysis showed respective sequencing similarities of 99 and 100% for 803 nucleotides of the Gp43 gene and 592 nucleotides from the ITS-5.8S region of Paracoccidioides brasiliensis. Immunohistochemistry revealed severe lymphadenitis and presented numerous yeasts, which reacted against the gp43 antibody. Histopathology revealed a severe granulomatous lymphadenitis associated with numerous single or multiple budding yeasts. After diagnosis, the dog was successfully treated with itraconazol for 2 years. Veterinarians should be aware of the importance of considering PCM for differential diagnosis, especially in dogs from PCM-endemic areas, whose monophagocytic system involvement is evident.

Background: Identifying clusters of acute paracoccidioidomycosis cases could potentially help in identifying the environmental factors that influence the incidence of this mycosis. However, unlike other endemic mycoses, there are no published reports of clusters of paracoccidioidomycosis., Methodology/principal Findings: A retrospective cluster detection test was applied to verify if an excess of acute form (AF) paracoccidioidomycosis cases in time and/or space occurred in Botucatu, an endemic area in São Paulo State. The scan-test SaTScan v7.0.3 was set to find clusters for the maximum temporal period of 1 year. The temporal test indicated a significant cluster in 1985 (P<0.005). This cluster comprised 10 cases, although 2.19 were expected for this year in this area. Age and clinical presentation of these cases were typical of AF paracccidioidomycosis. The space-time test confirmed the temporal cluster in 1985 and showed the localities where the risk was higher in that year. The cluster suggests that some particularities took place in the antecedent years in those localities. Analysis of climate variables showed that soil water storage was atypically high in 1982/83 ( approximately 2.11/2.5 SD above mean), and the absolute air humidity in 1984, the year preceding the cluster, was much higher than normal ( approximately 1.6 SD above mean), conditions that may have favored, respectively, antecedent fungal growth in the soil and conidia liberation in 1984, the probable year of exposure. These climatic anomalies in this area was due to the 1982/83 El Niño event, the strongest in the last 50 years., Conclusions/significance: We describe the first cluster of AF paracoccidioidomycosis, which was potentially linked to a climatic anomaly caused by the 1982/83 El Niño Southern Oscillation. This finding is important because it may help to clarify the conditions that favor Paracoccidioides brasiliensis survival and growth in the environment and that enhance human exposure, thus allowing the development of preventive measures.

Background: Paracoccidioidomycosis (PCM) is Latin America's most prevalent systemic mycosis, carrying an important social burden. Its agent, Paracoccidioides brasiliensis, has rarely been identified in nature. Studies characterizing acute/subacute PCM incidence and their relationship with climate variables are not available. This work analysed a series of acute/subacute cases that occurred in the Botucatu area, São Paulo State, Brazil, from 1969 to 1999, as an outcome of weather variability., Methods: Stepwise regression of annual data was applied to model incidence, calculated based on 91 cases, from lagged variables: antecedent precipitation, air temperature, soil water storage, absolute and relative air humidity, and Southern Oscillation Index (SOI)., Results: Multiple regression analyses resulted in a model, which explains 49% of the incidence variance, taking into account the absolute air humidity in the year of exposure, soil water storage and SOI of the previous 2 years., Conclusions: The correlations may reflect enhanced fungal growth after increase in soil water storage in the longer term and greater spore release with increase in absolute air humidity in the short term.

A recent species status investigation of the pathogenic fungus Paracoccidioides brasiliensis suggested the existence of three cryptic species. In the present study, the sequences of the PRP8 intein from P. brasiliensis isolates belonging to the three described genetic groups and two unidentified isolates were determined and analyzed in order to check their functionality and usefulness for species identification. All the isolates presented a full-length intein, although the Endonuclease domain seems to be inactive due to substitutions in the second essential aspartic acid residue. Phylogenetic analysis by Maximum-Parsimony, Maximum Likelihood, and Bayesian analysis clearly separated the isolates from the three species and revealed a significant difference between the Pb01 isolate and the remaining ones. The Pb01 isolate does not belong to any of the groups previously described since it presented a high divergence level compared to the three different genetic groups, corroborating some previous studies that suggested this isolate represents a new species of Paracoccidioides.

The knowledge on the biological aspects of Paracoccidioides brasiliensis has evolved greatly since the first description of the disease in 1908. From the pioneers, who were able to clearly demonstrate the fungal nature of the agent, to the recent genomic era, important advances have been achieved. P. brasiliensis is a true fungus, belonging to the Ascomycetous Division, although its sexual phase has not been demonstrated morphologically. A better understanding of the fundamental aspects of the agent, especially its phylogeny and evolutionary history, will provide us with valuable insights allowing a better comprehension of the disease and our capacity to deal with the problem. Concerning the fungus's ecology, although some progress had been observed, the ecological niche of the pathogen has not been determined yet. The aim of the present review is to focus on the biological aspects of P. brasiliensis from an evolutionary point of view, addressing the fungus's phylogenetic aspects, in those special points that might be relevant for the pathogen/host interactions, the biological forces that have been acting on its origin and maintenance of virulence, as well as in determining the fungus's ecology and epidemiology.

Paracoccidioides brasiliensis infections have been little studied in wild and/or domestic animals, which may represent an important indicator of the presence of the pathogen in nature. Road-killed wild animals have been used for surveillance of vectors of zoonotic pathogens and may offer new opportunities for eco-epidemiological studies of paracoccidiodomycosis (PCM). The presence of P. brasiliensis infection was evaluated by Nested-PCR in tissue samples collected from 19 road-killed animals; 3 Cavia aperea (guinea pig), 5 Cerdocyon thous (crab-eating-fox), 1 Dasypus novemcinctus (nine-banded armadillo), 1 Dasypus septemcinctus (seven-banded armadillo), 2 Didelphis albiventris (white-eared opossum), 1 Eira barbara (tayra), 2 Gallictis vittata (grison), 2 Procyon cancrivorus (raccoon) and 2 Sphiggurus spinosus (porcupine). Specific P. brasiliensis amplicons were detected in (a) several organs of the two armadillos and one guinea pig, (b) the lung and liver of the porcupine, and (c) the lungs of raccoons and grisons. P. brasiliensis infection in wild animals from endemic areas might be more common than initially postulated. Molecular techniques can be used for detecting new hosts and mapping 'hot spot' areas of PCM.

Paracoccidioides brasiliensis causes paracoccidioidomycosis (PCM) that is one of the most prevalent systemic human mycoses in Latin America. Armadillos show a high incidence of PCM infection and could, therefore, be a natural reservoir for this fungus. In this study were compared the virulence profiles of isolates obtained from nine-banded armadillos (Dasypus novemcinctus) (PbT1 and PbT4) and isolates from PCM patients (Pb265 and Bt83). Pathogenicity was evaluated by fungal load and analysis of colony morphology. Immunity against the fungus was tested by delayed type hypersensitivity test (DTH) and antibody quantification by ELISA. The higher virulence of PbT1 and PbT4 was suggested by higher fungal load in spleen and lungs. Armadillo isolates and Bt83 presented a cotton-like surface contrasting with the cerebriform appearance of Pb265. All isolates induced cellular and humoral immune responses in infected BALB/c mice. DTH reactions were similarly induced by the four isolates, however, a great variability was observed in specific antibody levels, being the highest ones induced by Bt83 and PbT4. The present work confirms that armadillos harbor P. brasiliensis, whose multiplication and induced immunity in experimentally infected mice are heterogeneous, resembling the behavior of isolates from human PCM. This study reinforces the possibility that armadillos play an important role in the biological cycle of this pathogen.

The habitat of the mycelial saprobic form of Paracoccidioides brasiliensis, which produces the infectious propagula, has not been determined and has proven difficult for mycologists to describe. The fungus has been rarely isolated from the environment, the disease has a prolonged latency period and no outbreaks have been reported. These facts have precluded the adoption of preventive measures to avoid infection. The confirmation of natural infections in nine-banded armadillos (Dasypus novemcinctus) with P. brasiliensis, in high frequency and wide geographic distribution, has opened new avenues for the study and understanding of its ecology. Armadillos belong to the order Xenarthra, which has existed in South America ever since the Paleocene Era (65 million years ago), when the South American subcontinent was still a detached land, before the consolidation of what is now known as the American continent. On the other hand, strong molecular evidence suggests that P. brasiliensis and other dimorphic pathogenic fungi--such as Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum--belong to the family Onygenaceae sensu lato (order Onygenales, Ascomycota), which appeared around 150 million years ago. P. brasiliensis ecology and relation to its human host are probably linked to the fungal evolutionary past, especially its long coexistence with and adaptation to animal hosts other than Homo sapiens, of earlier origin. Instead of being a blind alley, the meaning of parasitism for dimorphic pathogenic fungi should be considered as an open two-way avenue, in which the fungus may return to the environment, therefore contributing to preserve its teleomorphic (sexual) and anamorphic (asexual) forms in a defined and protected natural habitat.

Paracoccidioidomycosis (PCM) is endemic in Latin America and in countries like Brazil it carries a high mortality rate. The fungus' habitat has not been precisely determined. The present study aims to identify ecologic correlates based on PCM distribution in a hyper-endemic area in southeastern Brazil. The Geographic Information System (GIS) and spatial statistics were used to associate environmental attributes, human population density and, PCM distribution. By means of the Pearson r correlation coefficient, the highest statistically significant associations with prevalence density were the percent area (by county) of: basaltic rocks (r=0.63; P <0.0001), Podzolic soils (r= -0.48; P <0.001), Latosol soils (r=0.40; P <0.01), mean annual precipitation between 1500 and 1600 mm (r = 0.46; P < 0.001) and, mean precipitation during the wet season between 940 and 1040 mm (r= -0.44; P <0.01). Soil texture and precipitation analyzed together reached r=0.61 (P <0.000002) for fine-textured soils with annual precipitation above 1400 mm. Environmental correlates indicate that moisture availability plays an important role in PCM distribution.

Paracoccidioidomycosis (PCM) is the main and most prevalent systemic mycosis in Latin America, that until recently, it was believed to be caused only by Paracoccidioides brasiliensis (P. brasiliensis). In 2006, researchers described three cryptic species: S1, PS2, PS3, and later, another one, PS4. In 2009, Paracoccidioides lutzii (Pb01-like) was described, and in 2017, a new nomenclature was proposed for the different agents: P. brasiliensis (S1), P. americana (PS2), P. restrepiensis (PS3), and P. venezuelensis (PS4). These species are not uniformly distributed throughout Latin America and, knowing that more than one cryptic species could coexist in some regions, we aimed to identify those species in patients' biopsy samples for a better understanding of the distribution and occurrence of these recently described species in Botucatu region. The Hospital of Medical School of Botucatu—UNESP, which is a PCM study pole, is located in São Paulo State mid-west region and is classified as a PCM endemic area. Genotyping analyses of clinical specimens from these patients that have been diagnosed and treated in our Hospital could favor a possible correlation between genetic groups and mycological and clinical characteristics. For this, molecular techniques to differentiate Paracoccidioides species in these biopsies, such as DNA extraction, PCR, and sequencing of three target genes (ITS, CHS2, and ARF) were conducted. All the sequences were analyzed at BLAST to testify the presence of P. brasiliensis. The phylogenetic trees were constructed using Mega 7.0 software and showed that 100% of our positive samples were from S1 cryptic species, therefore P. brasiliensis. This is important data, demonstrating the predominance of this species in the São Paulo State region. [ABSTRACT FROM AUTHOR]

Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Brazil. The disease is caused by dimorphic fungi nested within the Paracoccidioides genus. We described 106 PCM cases (47.1 cases/year) at the Tropical Diseases Public Hospital of Tocantins State. PCM was prevalent in males and rural workers over 50 years; the chronic pulmonary form predominated in 67% of cases. The male-to-female ratio was 2.65:1, with more women affected than other endemic regions of Brazil. Urban or indoor activities were reported in women and are ascribed to disease urbanization. qPCR-based assays confirmed the identification of Paracoccidioides DNA in 37 biological specimens. Paracoccidioides sp. DNA was found in 53% of the environmental samples, suggesting autochthonous infections. Therefore, the Tocantins-Araguaia basin must be considered a novel hyperendemic area of PCM in Brazil, reinforcing the importance of including PCM as a notifiable disease, requiring specific diagnosis and health measures. [ABSTRACT FROM AUTHOR]

Paracoccidioidomycosis is an endemic fungal disease to Latin America caused by at least five species-level genotypes of Paracoccidioides, named P. lutzii, P. brasiliensis (S1a and S1b populations), P. americana, P. restrepiensis, and P. venezuelensis. In this manuscript, we report on Paracoccidioides sp. sampling efforts in armadillos from two different areas in Brazil. We sequenced the genomes of seven Paracoccidioides isolates and used phylogenomics and populations genetics for genotyping. We found that P. brasiliensis and P. lutzii are both present in the Amazon region. Additionally, we identified two Paracoccidioides isolates that seem to be the result of admixture between divergent populations within P. brasiliensis sensu stricto. Both of these isolates were recovered from armadillos in a P. lutzii endemic area in Midwestern Brazil. Additionally, two isolates from human patients also show evidence of resulting from admixture. Our results suggest that the populations of P. brasiliensis sensu stricto exchange genes in nature. More generally, they suggest that population structure and admixture within species is an important source of variation for pathogenic fungi. [ABSTRACT FROM AUTHOR]

Dear Editor Paraccoccidioidomycosis (PCM) is an endemic disease caused by the fungus I Paracoccidioidomycosis brasilensis i ,1,2 which when inhaled intensely and/or continuously reaches terminal bronchioles and alveoli promoting, in most of the cases, primary pulmonary paracoccidioidomycosis (PPCM).2,3 While effective treatment is available to control PPCM, many patients considered clinically cured have developed pulmonary hypertension (PH). Vascular adventitial layer collagen fibers deposition was significantly increased in PCM patients compared to the chronic obstructive pulmonary disease (COPD)/emphysema group without PH ( I P i < .05)(Figure 2), although COPD/emphysema is a known cause of vascular remodeling. GLO:F2H7/01nov20:ctm2213-fig-0002.jpg PHOTO (COLOR): 2 Human pulmonary paracoccidioidomycosis induced pulmonary hypertension. lung biopsy from PPCM patients and timeframe for development of pulmonary hypertension. [Extracted from the article]

Paracoccidioides brasiliensis complex and P. lutzii are the etiological agents of paracoccidioidomycosis. The geographic distribution of these species in South America is still poorly comprehended. Fifty samples of Paracoccidioides spp. were genotyped, with 46 clinical isolates predominantly isolated in the geographic area of Ribeirão Preto, SP, and four environmental isolates collected in Ibiá, MG, southeastern Brazil. These isolates were evaluated by PCR-RFLP (Restriction Fragment Length Polymorphism) of the tub1 gene and the sequencing of the gp43 exon 2 loci. The species P. lutzii was confirmed by sequencing the internal transcribed spacer (ITS) region of the ribosomal DNA. P. brasiliensis sensu stricto S1b (n = 42) and S1a (n = 5), P. americana (n = 1), P. restrepiensis (n = 1), and P. lutzii (n = 1) were identified among the clinical isolates. All the environmental isolates were characterized as P. brasiliensis sensu stricto S1b. The patient infection by P. lutzii, P. americana (PS2), and one isolate of P. brasiliensis sensu stricto S1b most likely occurred in a geographic area far from the fungal isolation site. No association was found between the infecting genotype and the disease form. These results expand the knowledge of the Paracoccidioides species distribution and emphasize that human migration must also be considered to pinpoint the genotypes in the endemic area. [ABSTRACT FROM AUTHOR]

Paracoccidioidomycosis caused by Paracoccidioides lutzii is endemic in the Midwest of Brazil and its clinical spectrum is still little known due to the recent identification of this fungal species. A patient resident in Southeast Brazil, but who had lived for many years in the Midwest region, presented with skin injuries, chronic cough and bilateral adrenal involvement. Paracoccidioides spp. was isolated in culture from a skin lesion biopsy. This isolate was later identified as P. lutzii using gene sequencing. A favorable initial response to treatment with itraconazole was observed, but a few weeks later, the patient developed respiratory failure and worsening of lung lesions. Evaluation by computed tomography and echocardiography were suggestive of pulmonary arterial hypertension, and a bronchoscopic biopsy showed peribronchial remodeling. The patient completed the antifungal treatment but maintained the respiratory dysfunction. The reported case shows that P. lutzii can be isolated from patients in a geographic area far from the place of infection acquisition and that, as P. brasiliensis, it can cause adrenal injury and cardio-respiratory complications as a consequence of excessive necrosis and fibrosis. [ABSTRACT FROM AUTHOR]

Background: Paracoccidioides brasiliensis and Paracoccidioides lutzii are the etiological agents of Paracoccidioidomycosis (PCM), and are easily isolated from human patients. However, due to human migration and a long latency period, clinical isolates do not reflect the spatial distribution of these pathogens. Molecular detection of P. brasiliensis and P. lutzii from soil, as well as their isolation from wild animals such as armadillos, are important for monitoring their environmental and geographical distribution. This study aimed to detect and, for the first time, evaluate the genetic diversity of P. brasiliensis and P. lutzii for Paracoccidioidomycosis in endemic and non-endemic areas of the environment, by using Nested PCR and in situ hybridization techniques. Methods/Principal Findings: Aerosol (n = 16) and soil (n = 34) samples from armadillo burrows, as well as armadillos (n = 7) were collected in endemic and non-endemic areas of PCM in the Southeastern, Midwestern and Northern regions of Brazil. Both P. brasiliensis and P. lutzii were detected in soil (67.5%) and aerosols (81%) by PCR of Internal Transcribed Spacer (ITS) region (60%), and also by in situ hybridization (83%). Fungal isolation from armadillo tissues was not possible. Sequences from both species of P. brasiliensis and P. lutzii were detected in all regions. In addition, we identified genetic Paracoccidioides variants in soil and aerosol samples which have never been reported before in clinical or armadillo samples, suggesting greater genetic variability in the environment than in vertebrate hosts. Conclusions/Significance: Data may reflect the actual occurrence of Paracoccidioides species in their saprobic habitat, despite their absence/non-detection in seven armadillos evaluated in regions with high prevalence of PCM infection by P. lutzii. These results may indicate a possible ecological difference between P. brasiliensis and P. lutzii concerning their wild hosts. [ABSTRACT FROM AUTHOR]

Paracoccidioides lutzii, formerly known as ‘Pb01-like’ strains in the P. brasiliensis complex, is proposed as a new species based on phylogenetic and comparative genomics data, recombination analysis, and morphological characteristics. Conidia of P. lutzii are elongated, different from those of P. brasiliensis. P. lutzii occurs in the central and northern regions of Brazil. Studies comparing P. brasiliensis and P. lutzii may have significant clinical consequences for the diagnosis and treatment of paracoccidioidomycosis. [ABSTRACT FROM PUBLISHER]

Abstract: This work was conducted to identify virulence biomarkers for Paracoccidioides brasiliensis (Pb), the fungus responsible for Paracoccidioidomycosis (PCM), a systemic disease endemic in Latin America. Measurement of mortality showed that all B10.A mice were killed after 250 days by the virulent Pb18 isolate while only one of the mice that received the attenuated counterpart died. Also, number of lung CFUs from virulent Pb18 inoculated mice were much higher when these isolates were compared. Phage display methodology allowed selection of three phages that specifically bound to virulent Pb18. Variability of p04 phage binding to different Pb isolates were examples of variability of expression by the fungus of its binding molecule, strongly suggesting p04 as a biomarker of virulence. In vitro, its derived peptide pep04 killed only virulent fungi, and confocal microscopy showed that it was internalized only by the virulent isolate. Pep04 blocked establishment of Pb infection in mice and virulent Pb18 pre-incubated with p04 showed significantly inhibited lung infection. Furthermore, infected mice treated with p04 showed highly significant reduction in lung CFUs. These findings firmly establish p04 as a biomarker of Pb virulence. Therefore, after proper peptide engineering, p04 may become a useful adjuvant for the distressing treatment of PCM. [Copyright &y& Elsevier]